Elevation of beta-adrenergic receptor density in human lymphocytes after propranolol administration.

Abstract

A B S T R A C T Abrupt withdrawal after the chronic administration of propranolol has resulted in clinical syndromes that suggest adrenergic hypersensitivity. The effect of propranolol administration and withdrawal on ,-adrenergic receptors was studied in human lymphocyte membranes. Receptor density was quantitated by direct binding assays with the radioligand [1251]iodohydroxybenzylpindolol. Administration ofpropranolol (160 mg/d) for 8 d resulted in trough plasma levels of -35 ng/ml. By day 5 ofpropranolol administration the density of /3-adrenergic receptors had increased 43+4% (P < 0.01) above pretreatment levels. Abrupt withdrawal of propranolol was followed by the disappearance of propranolol from the plasma within 24 h. The density of f3-adrenergic receptors did not return to pretreatment level for several days. Physiologic supersensitivity of 8-adrenergic receptor-mediated responses was suggested by the appearance of significant increases in the orthostatic change in heart rate (P < 0.05) and the orthostatic change in the heart rate-systolic blood pressure product (P < 0.01) during the first 48 h after propranolol withdrawal. These data show that propranolol administration leads to an increase in the density of f3-adrenergic receptors in human tissue. The results are consistent with the hypothesis that some of the untoward effects observed after abrupt discontinuation of propranolol are caused by 8-receptor-mediated adrenergic hypersensitivity.

Chronic Administration of KB-R7943 Induces Up-regulation of Cardiac NCX1

“…Chronic administration of anti-arrhythmic drugs, which inhibit the fast Na ϩ channel, results in the up-regulation of Na ϩ channel expression in cardiomyocytes (45). Furthermore, it has long been understood that inhibition of ␤-adrenergic receptor activity leads to increases in the density of ␤-adrenergic receptors present in the cell (29). Interestingly, the withdrawal of ␤-blockers has been found to greatly increase the risk of unstable angina, myocardial infarction, and sudden death (46,47).…”

“…Prolonged blockade of L-type calcium channels, ␤-adrenergic receptors, or the Na ϩ /H ϩ exchanger results in their up-regulation (27,28). In light of what occurs with chronic inhibition of several cardiac channels, receptors, and exchangers (29), we investigated whether chronic inhibition of NCX1 activity had any effect on the expression of Ncx1 in cardiomyocytes. This is an important consideration given the potential of NCX1 inhibition as part of a future therapeutic approach.…”

Intérêt des bêta-bloquants en médecine périopératoire. Première partie: notions fondamentales

“…Un phénomène inverse intervient si la stimulation agoniste diminue ou si le récepteur est occupé par un BB. 3 Ces phénomènes permettraient d'expliquer les manifestations de "rebond" à l'arrêt brutal d'un BB et de comprendre qu'au cours des insuffisances cardiaques graves, la densité des bêta-récepteurs est diminuée par une intense stimulation adrénergique.…”

Pindolol‐a beta‐adrenoceptor blocking drug with partial agonist activity: clinical pharmacological considerations.

“…This has been attributed to an increase in P-adrenoceptor density during chronic 3-adrenoceptor blockade (Aarons et al, 1980). During the administration of f-adrenoceptor stimulant drugs the opposite effect,…”